chr7-74059905-CGTGGCTCCTGGAGTTGGCGTGGCTCCTGGTGTCGGT-C

Variant names:

• chr7-74059905-CGTGGCTCCTGGAGTTGGCGTGGCTCCTGGTGTCGGT-C
• rs782202364
• NM_000501.4:c.1453_1488delGTGGCTCCTGGTGTCGGTGTGGCTCCTGGAGTTGGC

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3 BP6 BS2

The NM_000501.4(ELN):​c.1453_1488delGTGGCTCCTGGTGTCGGTGTGGCTCCTGGAGTTGGC​(p.Val485_Gly496del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000988 in 151,854 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ELN NM_000501.4 conservative_inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: 3.24
• Publications: 0 publications found

Genes affected

ELN (HGNC:3327): (elastin) This gene encodes a protein that is one of the two components of elastic fibers. Elastic fibers comprise part of the extracellular matrix and confer elasticity to organs and tissues including the heart, skin, lungs, ligaments, and blood vessels. The encoded protein is rich in hydrophobic amino acids such as glycine and proline, which form mobile hydrophobic regions bounded by crosslinks between lysine residues. Degradation products of the encoded protein, known as elastin-derived peptides or elastokines, bind the elastin receptor complex and other receptors and stimulate migration and proliferation of monocytes and skin fibroblasts. Elastokines can also contribute to cancer progression. Deletions and mutations in this gene are associated with supravalvular aortic stenosis (SVAS) and autosomal dominant cutis laxa. [provided by RefSeq, Aug 2017]

ELN-AS1 (HGNC:40212): (ELN antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_000501.4
• BP6: Variant 7-74059905-CGTGGCTCCTGGAGTTGGCGTGGCTCCTGGTGTCGGT-C is Benign according to our data. Variant chr7-74059905-CGTGGCTCCTGGAGTTGGCGTGGCTCCTGGTGTCGGT-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1178166.
• BS2: High AC in GnomAd4 at 15 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000501.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELN	NM_000501.4	MANE Select	c.1453_1488delGTGGCTCCTGGTGTCGGTGTGGCTCCTGGAGTTGGC	p.Val485_Gly496del	conservative_inframe_deletion	Exon 23 of 33	NP_000492.2	P15502-2
	ELN	NM_001278939.2		c.1540_1575delGTGGCTCCTGGTGTCGGTGTGGCTCCTGGAGTTGGC	p.Val514_Gly525del	conservative_inframe_deletion	Exon 24 of 34	NP_001265868.1	P15502-3
	ELN	NM_001278915.2		c.1471_1506delGTGGCTCCTGGTGTCGGTGTGGCTCCTGGAGTTGGC	p.Val491_Gly502del	conservative_inframe_deletion	Exon 23 of 33	NP_001265844.1	P15502-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELN	ENST00000252034.12	TSL:1 MANE Select	c.1453_1488delGTGGCTCCTGGTGTCGGTGTGGCTCCTGGAGTTGGC	p.Val485_Gly496del	conservative_inframe_deletion	Exon 23 of 33	ENSP00000252034.7	P15502-2
	ELN	ENST00000380562.8	TSL:1	c.1471_1506delGTGGCTCCTGGTGTCGGTGTGGCTCCTGGAGTTGGC	p.Val491_Gly502del	conservative_inframe_deletion	Exon 23 of 33	ENSP00000369936.4	P15502-1
	ELN	ENST00000458204.5	TSL:1	c.1423_1458delGTGGCTCCTGGTGTCGGTGTGGCTCCTGGAGTTGGC	p.Val475_Gly486del	conservative_inframe_deletion	Exon 22 of 32	ENSP00000403162.1	E7EN65

Frequencies

GnomAD3 genomes AF: 0.0000989 AC: 15 AN: 151736 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000596 AC: 15 AN: 251468 AF XY: 0.0000441

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000105

Gnomad OTH exome AF: 0.000163

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000142 AC: 182 AN: 1280740 Hom.: 0 AF XY: 0.000145 AC XY: 94 AN XY: 646406

African (AFR) AF: 0.0000668 AC: 2 AN: 29918

American (AMR) AF: 0.0000449 AC: 2 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24978

East Asian (EAS) AF: 0.00 AC: 0 AN: 38836

South Asian (SAS) AF: 0.000109 AC: 9 AN: 82746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.000184 AC: 1 AN: 5436

European-Non Finnish (NFE) AF: 0.000154 AC: 146 AN: 946726

Other (OTH) AF: 0.000406 AC: 22 AN: 54246

GnomAD4 genome AF: 0.0000988 AC: 15 AN: 151854 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74190

African (AFR) AF: 0.00 AC: 0 AN: 41386

American (AMR) AF: 0.0000656 AC: 1 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67954

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.0000508 Hom.: 0

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	1	-	Supravalvar aortic stenosis (1)
-	1	-	Supravalvar aortic stenosis;C3276539:Cutis laxa, autosomal dominant 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
Mutation Taster		=162/38	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs782202364; hg19: chr7-73474235;